1
Q
Growth Hormone
A
released from anterior pituitary
stimulated by GHRH
inhibited by somatostatin
target organs: liver/bone/muscles
regulated growth and metabolic rate
2
Q
Adrenocorticotrophic hormone (ACTH)
A
stimulated by corticotrophin-releasing hormone
target organ adrenal gland
stimulates release of cortisol
3
Q
Follicle stimulating hormone
A
Stimulated by GnRH
Target organ: gonads
Stimulates release of testosterone/oestrogen and production of eggs/sperm
4
Q
TSH
A
Stimulated by thyrotropin releasing hormones
Target thyroid gland
stimulates release of thyroid hormones T3/4
5
Q
Prolactin
A
Weakly stimulated by TRH, oxytocin and ADH
Inhibited by dopamine
Target organ mammary glands
Stimulates lactation
6
Q
Antidiuretic hormone
A
Released from posterior pituitary
Acts of collecting duct of kidneys
Increases water reabsorption
7
Q
Oxytocin
A
Released from posterior pituitary
Acts on female reproductive system
Stimulates milk ejection in suckling and uterine contractions in childbirth
8
Q
Hormones released from anterior pituitary
A
Growth Hormone
Adrenocorticotrophin hormone
Thyroid Stimulating hormone
FSH
LH
Prolactin
9
Q
Pituitary anatomy
A
- lies immediately beneath hypothalamus in bony hollow of sphenoid bone (sella turcica)
-optic chiasm lies directly superior to anterior pituitary - post pituitary connected to median emminence of hypothalamus by infundibulum
- cavernous sinuses (inc CN III, IV, V, VI) lie lateral to pituitary gland
10
Q
Anterior pituitary
A
released under control of hypothalamus releasing/inhibiting hormones into blood at median eminence
transported directly to anterior pituitary by hypophyseal vessels
negative feedback mechanisms
11
Q
Posterior pituitary
A
secretes oxytocin and ADH (peptide hormones)
manufactured in hypothalamus and transported for storage within pituitary
ADH = negative feedback
oxytocin = positive feedback
12
Q
Diabetes Insipidus
A
cranial DI - deficiency of ADH secretion
nephrogenic DI - inappropriate renal response to ADH
13
Q
Biochemical features DI
A
-high plasma osmolality >295
- low urine osmolality
- hypernatraemia
- polydipsia
14
Q
Cranial DI causes
A
inflammatory hypophysitis
histiocytosis X
post pituitary surgery
15
Q
Nephrogenic DI causes
A
metabolic or electrolyte disturbance
renal disease
drugs e.g. lithium
16
Q
ADH stimulation test
A
nephrogenic DI unable to concentrate urine post ADH stimulation
17
Q
SIADH diagnosis
A
euvolaemic hypo-osmolar hyponatraemia
- low serum osmolality
- urine osmolality >100
- urine sodium >30
only Dx after exclusion of hypothyroidism, total salt depletion and ACTH def
18
Q
Causes SIADH
A
malignancy
neurological - infection, trauma, malignancy, haemorrhage
pulmonary - pneumonia, TB, abscess, malignancy
drugs - SSRI, TCA, anticonvulsants
GBS, acute intermittent porphyria
19
Q
Adrenal function
A
Located on superior pole of kidney
retroperitoneal, enclosed in renal fascia
Adrenal cortex (outer) and adrenal medulla
20
Q
Adrenal cortex zones
A
zona glomerulosa - mineralocorticoid secretion (aldosterone), regulates salt and water homeostasis
zona fasciculata - glucocorticoid (cortisol), carb metabolism and stress response
zona reticularis - secretes androgen dehydroepiandrosterone (DHEA), maintenance of secondary sexual characteristics
DHEA and cortisol stimulated by ACTH (ant pit) - released in response to CRH from hypothal
Aldosterone regulated by RAAS in response to low circulating volume, hyponatraemia or hyperkalaemia
21
Q
Adrenal Medulla
A
Produces catecholaemines - adrenaline and noradrenaline in sympathetic nervous system
22
Q
Phaeochromocytoma
A
catecholamine secreting tumours
90% arise from adrenal medulla
10% from extra adrenal chromaffin tissue - paragangliomas
headache, sweating, pallor and palpitations
Dx elevated catecholamines or urine metanephrines
alpha blockade before beta blockade to reduce risk of hypertensive crisis
23
Q
Aldosterone
A
secreted by zona glomerulosa
release stimulated by angiotensin II, high plasma K+ and ACTH
mainly acts on DCT - causes sodium retention and potassium loss
increases Na reabsorption, K/H+ secretion
24
Q
Adrenaline/noradrenaline
A
released from adrenal medulla
act through G-protein coupled adrenoreceptors
a1, a1, b1-3
noradrenaline has equal potency at all receptors
adrenaline at normal plasma concs only acts on b receptors
25
Cortisol
released during normal physiological activity, pulsatile secretion, driven by CRH
primary stimulus for increased glucocorticoid release is stress - driven by amygdala
26
Amygdala
stress response
part of forebrain
stimulates:
- activity in hypothalamic CRH neurones
- activity in sympathetic nervous system
-activity in parasympathetic nervous system causing acid secretion in stomach
- feeling of fear
27
Stress response
catecholamines released from adrenal medulla - rapid increased in CO and mobilisation of metabolic fuels
corticosteroids produce slower more sustained response by:
- increasing glycolysis and gluconeogenesis
- reducing glucose transport into storage tissues
- increasing protein catabolism and release of amino acids
28
Cushing's syndrome
chronic excess glucocorticoids
causes:
- excess secretion of ACTH e.g. pituitary adenoma (cushing's disease) or ectopic ACTH
- excess secretion of cortisol by adrenal adenoma or carcinoma
- exogenous steroids
28
Pathological effects of chronic stress
depression - damage to nerve cells in hippocampus that are part of feedback loop in controlling stress response
increased susceptibility to infection ( anti-inflammatory effects)
chronic hypertension
peptic ulcers - increased gastric acid secretion
29
Cushing's disease
excess glucocorticoid as a result of ACTH secreting pituitary adenoma
causes bilateral adrenal hyperplasia and excess cortisol secretion
hyperpigmentation due to melanocyte-stimulating action of ACTH
30
Addison's Disease
all 3 zones affected
hyponatraemia, hyperkalaemia, hypoglycaemia, low morning cortisol
elevated ACTH
synacthen test
31
Hyperaldosteronism
Excessive level of aldosterone
- primary (independent of RAS)
- secondary (high renin levels)
increased sodium retention and therefore water retention and volume expansion, hypokalaemia
adrenal adenoma (conn's syndrome), adrenal hyperplasia, familial hyperaldosteronism, adrenal carcinoma
32
Endocrine pancreas function
islets of Langerhans
alpha cells - glucagon
beta cells - insulin
delta cells - somatostatin
epsilon cells - ghrelin
PP cells - pancreatic polypeptide
receive 10-15% pancreatic blood flow
33
Ghrelin
released by stomach (+small intestine, pancreas and brain)
stimultes appetite, increases food intake and promotes fat storage
acts on hypothalamus - control of appetite
reward processing in amygdala
stimulates GH
34
Insulin physiology
polypeptide hormone, 2 short chains linked by disulphide bonds
proinsulin synthesised as single chain peptide
within storage granules, connecting c-peptide removed by proteases -> insulin
c-peptide secreted along side insulin
35
Insulin stimulation
parasympathetic nervous stimulation during eating
secretin
rise in plasma glucose concentration
circulating fatty acids, ketone bodies and amino acids enhance effects of glucose
36
Insulin mechanism
Stimulate glucose uptake
subsequent manufacture of glycogen and triglycerides by adipose, muscle and liver cells
effects mediated by receptor tyrosine kinase
activates intracellular pathway resulting in translocation of GLUT-4 (and GLUT-1) to plasma membrane -> facilitate entry of glucose
release reduced and BM falls and inhibited by catecholamines and somatostatin
37
Insulin actions
increase glucose uptake
increase glycogenesis
decrease glycogenolysis
decrease gluconeogenesis
increase protein synthesis
increase fat deposition
reduce lipolysis
reduce ketoacid production
increase K+ uptake
38
Glycogen secretion
released by alpha cells
reduced BM
increased amino acids
cholecystokinin
catecholamines
acetylcholine
39
Glycogen reduced secretion
high blood glucose
insulin
somatostatin
fatty acids and ketoacids
40
Glycogen actions
reduce glycogenesis
increase glycogenolysis
increase gluconeogenesis
reduce fatty acid synthesis
increase lipolysis
increase ketoacid production
41
Diabetes mellitus type 1
autoimmune destruction of beta cells of pancreas results in absolute insulin deficiency
glucose unable to be transported in to cells via GLUT 4 transporter
42
Thyroid Gland anatomy
anterior neck below and lateral to thyroid cartilage
c5-t1
2 lateral lobes connected by isthmus - across anterior surface of 2nd and 3rd tracheal cartilages
43
Thyroid anatomy relations
deep to sternohyoid, sternothyroid and omohyoid
within visceral compartment of neck along with (anterior to) pharynx, trachea, oesophagus, surrounded by pretracheal fascia
vulnerable structures in thyroid surgery:
- thyroidea ima artery
- inferior thyroid vein
- anterior jugular vein
- recurrent laryngeal nerve
- cervical dome of pleura
- oesophagus
- parathyroid glands
44
Thyroid blood supply
predominantly superior thyroid artery (branch of external carotid)
inferior thyroid artery (branch of thyrocervical trunk from subclavian)
superior and middle thyroid veins drain into internal jugular
inferior thyroid ceins drain into brachiocephalic veins
lymph drainage to paratracheal nodes and deep cervical nodes
45
Recurrent Laryngeal Nerve
branches from vagus and loops subclavian artery on R and arch of aorta on L
ascends in neck in groove between trachea and oesophagus
pass deep to posteromedial surface of lateral lobes of thyroid gland
commonly injured in thyroid surgery
supplies innervation to laryngeal cavity below level of vocal folds and motor innervation to all intrinsic muscles of larynx EXCEPT cricothyroid muscle
46
Thyroid hormones
thyroid tissue made of colloid - contains iodinated thyroglobulin
thyroglobulin synthesised by follicular cells
thyroxine (T4) 5/6, triiodothyronine (T3) 1/6
T4 converted peripherally to T3 (more potent and shorter acting)
released under control of TSH from ant pit (regulated by TRH in hypothal) in response to thermoreceptor and metabolic signals
negative feedback
mostly bound to thyroxine binding protein, transthyretin and albumin
47
Physiological effects of thyroid hormones
maintain normal metabolic rate
heat production
increased basal metabolic rate
metabolic effects:
- increased protein turnover
- increase in lipolysos
- increase in glycogenolysis and gluconeogenesis
increase in HR, SV and CO
important role in growth and development
48
Parathyroid hormone
peptide hormone synthesised by chief cells of parathyroid gland
released in response to:
- decreasing plasma Ca2+ conc
- increasing blood PO43- conc
release inhibited by normal Ca and hypomagnesaemia
49
Effects of PTH
bone: increase calcium and phos resorption from bone - immediate stimulation of osteocytic osteolysis, later by upregulation of osteoclasts
kidneys: increase ca reabsorption in distal tubule - activates Ca 2+ entry channels in apical mem and Ca ATPase in basolateral
- increases phos excretion by inhibiting reasorptionin prox tub
inhibits HCO3- reabsorption stimulating metabolic acidosis
- stimulaes alpha hydroxylase in kidneys to produce activated vit D
gut: indirectly increase Ca and phos absorption in small intestine via activated vit D
50
Calcitonin
high plasma concentration of calcium stimulates parafollicular cells of thyroid to release calcitonin
stimulates osteoblasts
inhibits osteoclasts
calcium removed from blood to build bone
51
osteoporosis
reduced bone mass and increased bone fragility
oestrogen deficiency and aging
FH, smoking, alcohol, vit D def
52
processes to stop bleeding
vasoconstriction
platelet plug
coagulation
53
platelet aggregation
plts contain alpha granules and dense granules
injury to vessel wall exposing collagen -> platelet activation -> changes shape with pseudopodia, granules move to surface of cell
granules release ADP and TXA2
54
common coagulation pathway
factor X -> factor Xa - acts on prothrombin -> thrombin -> fibrinogen -> fibrin clot
55
intrinsic pathway
set off by collagen exposure
XII -> XI -> IX -> VIII
56
extrinsic pathway
tissue factor (within endothelial cells) -> VII
57
vitamin K dependent factors
II
VII
IX
X
58
fibrinolysis
t-PA (tissue plasminogen activator) released slowly from endothelial cells
plasminogen caught in fibrin clot
t-PA acts on plasminogen -> plasmin -> breaks down fibrin
59
prothrombin time
measure of extrinsic pathway
expressed as INR
prolonged by warfarin
vit K deficiency
liver disease
DIC
60
activated partial thromboplastin time (APTT)
tests for abnormalities in intrinsic pathway
prolonged by heparin treatment, haemophilia, DIC, liver disease
61
platelet disorders - decreased production
aplastic anaemia
marrow infiltration e.g. leukaemia, myeloma
marrow suppression e.g. cytotoxic drugs, radiotherapy
62
platelet disorders - increased destruction
immune thrombocytopenia e.g. SLE, CLL, drugs e.g. heparin (HIT), viruses
non immune e.g DIC, haemolytic uraemic syndrome
poorly functioning platelets - myeloproliferative disease, NSAIDs, increased urea
63
Coagulation disorders congenital
haemophilia A - VIII deficiency (last factor in intrinsic pathway)
- sex linked inheritance
- treatment with recombinant factor VIII
haemophilia B - Christmas disease, factor IX deficiency
- clinically similar, recombinant factor IX
von Willebrand's disease
- deficient or abnormal vWF
- important in platelet adhesion to collagen and other platelets
64
anticoagulants: heparin
- occurs naturally in body in basophils and mast cells
- act indirectly by binding antithrombin III
unfractionated heparin: given IV, binds antithrombin -> increases ability to inhibit thrombin, factor Xa and IXa
monitor APTT
antidote protamine sulfate
safer in renal disease
65
LMWH
inactive factor Xa
longer half life
response is more predictable
66
fondaparinux
pentasaccharide
Xa inhibitor
lower risk of HIT
67
warfarin
long term anticoagulant
vit k antagonist
reversal:
- vit K hours to work, can cause prolonged resistance on restarting warfarin
- FFP used in warfarin overdose
- prothrombin complex concentrate contains factors II VII IX X
68
DOACs
direct thrombin inhibitor -> dabigatran
direct factor Xa inhibitors -> apixaban
69
thrombophilia
inherited:
- factor V leiden
- protein C and S deficiency - involved in neutralising clotting factors
- antithrombin III deficiency
acquired
- antiphospholipid syndrome -> linked to SLE (lupus anticoagulant), anticardiolipin antibody
- oral contraceptive pill
- HRT
- polycythaemia
- malignancy
- pregnancy
- obesity
70
types of anaemia
microcytic
normocytic
macrocytic
haemolytic
71
microcytic
- iron deficiency
- thalassaemia
72
normocytic anaemia
anaemia of chronic disease
bone marrow failure
renal failure (reduced EPO production)
haemolysis
73
macrocytic
B12 and folate deficiency
alcohol excess or liver disease
reticulocytosis
pregnancy
drugs e.g. phenytoin
megaloblasts in marrow
low Hb high MCV
hypersegmented neutrophils
74
IDA
blood loss
malabsorption
koilonychia
atrophic glossitis
angular cheilosis
plummer-vinson syndrome (difficulty swallowing, webs across endothelium)
blood film: microcytic, hypochromic anaemia with anisocytosis and poikilocytosis
Low MCV, low MCH and MCHC
confirmed by low ferritin
75
macrocytic anaemia - folate
hypersegmented neutrophils
high MCV
folate: essential for DNA formation, found in plants and meats, common in coeliac or crohn's
neural tube defects
76
B12 deficiency
B12: essential for DNA production, mostly absorbed from meat, important in myelin productions - cause CNS problems
- dietary e.g. vegans
- failure to absorb B12 - gastric disease, disease of terminal ileum
features:
- neuropsychiatric: irritability, depression, psychosis, dementia
- neurological: loss of motor and sensory function, dorsal column damage (subacute combined degeneration of spinal cord)
if folate and B12 deficient - if given folate without B12 can precipitate worsening B12 deficiency and cause neurological damage
77
haemolytic anaemia
premature breakdown of RBCs
intravascular or RES e.g. macrophages in liver, spleen and bone marrow
jaundice
hepatosplenomegaly
gallstones (pigment stones)
coombs test:
- direct coombs test - detects antibodies already bound to RBCs, test with antiserum -> binds human immunoglobulin to see if agglutinates
used in haemolytic anaemia testing
- indirect coombs test:
looks at plasma to see if antibodies circulating that may bind RBCs
used in prenatal testing
78
haemolytic anaemia causes
acquired:
1. immune-mediated (coombs +ve) - drug induced e.g. penicillin, quinine
autoimmune - warm and cold antibodies
prosthetic heart valves
hereditary
- G6PD deficiency
- membrane defects e.g. hereditary spherocytosis or elliptocytosis
- haemoglobinopathy e.g. sickle-cell or thalassaemia
79
G6PD deficiency
Commonest RBC enzyme defect
mediterranean, africa, middle east
mostly asymptomatic
precipitated by drugs e.g primaquine, sulphonamides, aspirin, exposure to broad beans/favism, illness
sex linked
80
sickle cell anaemia
abnormal Hb
HbS (abnormal substitution of 6th amino acid) instead of HbA
problem in hypoxia
Hb polymerises and distorts shape of red cell
heterozygotes - rarely affected
homozygotes
during relative hypoxia sickle cells haemolyse and block small vessels -> vaso-occlusive crises
sickle cells, target cells
81
Clinical features of sickle cell
painful crises (vaso-occlusive)
- bone pain (sites of haemopoiesis - adults axial skeleton, children long bones)
- triggered by cold, dehydration, infection, hypoxia
aplastic crisis - much higher turnover over RBCs (lifespan only 7days), if anything stops making red cells become anaemic quickly
precipitated by parvovirus B19
sickle lung syndrome - vasocclusive episodes within lungs, shadowing and hypoxia
splenic infarction - infection risk, particularly pneumonia
osteomyelitis
dactylitis
stroke
avascular necrosis
priapism
82
thalassaemia
genetic diseases with unbalanced Hb synthesis
alpha thalassaemia: decreased or absent alpha chain production
- 4 alleles affected = fatal
- 3 alleles affected - HbH disease
beta thalassaemia:
- if one allele affected (thalassaemia minor), usually asymptomatic
- tend to have increased HbA2 >3.5% and slight increase in HbF
- both alleles affected - thalassaemia major
- severe anaemia from childhood
- splenomegaly
- iron overload
83
Ventricular AP
resting potential -90mV
phase 0 = fast voltage gated Na channels -> rapid upstroke
phase 1 peak AP +10-20mV, closing of voltage gated Na, partial repolarisation
Phase 2 plateau phase -> slow L-type Ca channels open - influx Ca, balanced by K efflux leak
phase 3 end of plateau phase - Ca channels close, rapid K efflux -> repolarises membrace
phase 4 K efflux returns membrane potential to rest
84
Excitation-contraction coupling
Ca influx during plateau phase -> binds to troponin C -> conformational change in troponin-tropomyosin complex -> tropomyosin moves out of actin filament grove exposing myosin -> myosin heads bind to actin filaments
85
SA node potentials
threshold value -45 to -55mV, pacemaker potential
phase 0 - opening of slow voltage gated T-type Ca channels, close roughly 0mV
phase 3 - closure of Ca channels, opening of K+ channels - repolarisation
phase 4 - spontaneous depolarisation via Na and L type Ca channels, slope of phase 4 determines HR
86
autonomic control of pacemaker potential
norad and adr act on Gs protein coupled receptors -> increased cAMP -> increased Ca channel opening
+ve chronotropic
parasympathetic stim - Ach acts on muscarinic receptors, opposite effect
87
p wave
atrial depolarisation
downward and leftward current movement
usually positive in all limb leads
88
Q wave
interventricular septal depolarisation
initial depolarisation of left bundle cases current movement from L -> R in upper septum
small negative deflection at onset of QRS complex
89
R wave
early ventricular depolarisation
strongly downward and leftward spread of depolarisation through bundle branches to apex of heart and into ventricular muscle
positive deflection usually in all 3 limb leads
90
S wave
late ventricular depolarisation
depolarisation spreading throughout myocardium from apex back superiorly
negative deflection below baseline, particularly II and III
91
T wave
ventricular repolarisation
repolarising current
positive deflection in most leads
AVR and V1 inverted
92
normal axis
-30 to +90 degrees
93
L axis deviation
between -90 and -30
LVH
L anterior fascicular block
94
R axis deviation
+180 to +90
L posterior fascicular block
RVH
Chronic lung disease
acute RV strain
95
chest leads
V1-V6
unipolar leads
look at heart in horizontal plane
direction of cardiac impulse in horizontal plan A -> P
= R wave progression (becomes less negative to and more positive)
failure of R wave progression = early sign of ischaemia
96
causes of upright R wave in V1
RBBB
posterior MI
RVH
97
anatomical location MI
anterior wall = LAD = V2-4
septal = LAD = V1-2
lateral = L circumflex = V5-6, I, aVL
extensive anterior = prox L coronary = V2-V6, I, aVL
inferior = RCA = II, III, aVF
RA = SA node: RCA 60%, LCx 40%, AV node: RCA 90% LAD 10% = I, II, III
true posterior = LCx/RCA = ST depression and upward R wave V1/2, ST elevation in V7,8,9
RV = RCA = V1, aVL, aVF
98
ECG changes of myocardial infarction
early myocardial infarction - hyperacute T wave and failure of R wave progression
acute ST elevation
days: ST elevation, pathological Q waves, T wave inversion
weeks: ST segment flattens out
months: T waves correct, pathological Q waves persist, persistent ST elevation - may indicate LV aneurysm
99
hyperkalaemia ECG
tall, tented, narrow T waves
decreased P wave amplitude
widened QRS complex
AV block
absent P waves
very broad sinusoidal QRS
VT/VF
100
hypokalaemia ECG
widening T waves
prolonged PR
ST depression
U waves
ventricular ectopics, SVT/VT
MRCEM primary
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